Field of the Invention
The present invention relates to the manufacture of a capsule containing a biologically active medium, intended to be implanted in a living organism for therapeutic purposes. In the conventional way, a capsule of this type consists of a core comprising a biologically active medium, which is surrounded by a semipermeable casing. The role of the casing is to isolate the biologically active medium from the tissues of the receiving organism while at the same time allowing substances via which the implanted capsule fulfils its functions to pass through the casing. By way of example, when the biologically active medium is a suspension of cells, the semipermeable casing must act as a barrier to immune reactions, must allow nutrients to diffuse towards the core of the capsule and must allow the substance of therapeutic benefit secreted by the cells (insulin, for example, when the cells are islets of Langerhans) to diffuse towards the organism.
From the point of view of the efficiency of the exchanges across the membrane, it would seem that spherical capsules are preferred over tubular capsules. However, spherical capsules have the drawback of being difficult to locate when implanted, which means that at the present time it would not be possible to implant them in a human body from which the implants have always to be able to be extracted for reasons of biological safety.
Recent research has therefore been mainly centred on manufacturing tubular capsules, which allow the shaping of implants that are long enough that they can be easily found. In particular, it has been discovered that it is preferable to segment the tubular capsules, that is to say to form therein compartments which are isolated from one another, so that if part of an implanted capsule is damaged, it is possible to separate it from the implant and extract it from the receiving organism.
U.S. Pat. No. 5,158,881 describes a method of manufacturing a segmented tubular capsule, comprising the steps of:
coextruding a polymer solution intended to form the casing of the capsule and a biologically active medium by simultaneously injecting the polymer solution and the biologically active medium through a die, and PA1 interrupting the injection of the biologically active medium at determined points in time to form in the fibre successive compartments full of the biologically active medium and separated by a solid partition section consisting only of the polymer solution. PA1 coextruding the solution of at least one polymer and the biologically active medium by simultaneously injecting the polymer solution and the biologically active medium through a die of determined dimensions, PA1 interrupting the injection of the biologically active medium at determined points in time to form in the fibre successive compartments full of the biologically active medium and separated by a consisting partition section consisting made of of the polymer solution, PA1 causing partial early solidification of the fibre as it leaves the die to a sufficient extent to prevent the fibre from breaking at the partition sections. PA1 immersing the fibre in a coagulation liquid as it leaves the die so as to initiate early coagulation of the polymer solution around the outside of the fibre; and PA1 simultaneously driving the fibre through the coagulation liquid along a determined path. PA1 extrusion means of determined dimensions for coextruding a solution of at least one polymer and the biologically active medium in such a way as to obtain a tubular fibre having a wall made from the polymer solution and filled with the biologically active medium; PA1 means for supplying the extrusion means with the polymer solution and with the biologically active medium; PA1 means for controlling the simultaneous supply of the extrusion means with polymer solution and with biologically active medium and for interrupting the supply of biologically active medium at determined points in time so as to form within the fibre successive compartments filled with the biologically active medium and separated by a solid partition section consisting only of the polymer solution; PA1 means for causing partial solidification of the fibre as it leaves the extrusion means, this solidification being enough to prevent the fibre from breaking at the partition sections. PA1 a bath for a coagulation liquid placed under the extrusion means at a chosen distance so that a fibre flowing out from the die at a given output rate begins to coagulate early from the outside and does not break; and PA1 means for driving the fibre through the coagulation liquid along a determined path. PA1 a mandrel made up of disassemble portions; PA1 means for rotating the mandrel; PA1 a guiding device for moving the fibre with a back and forth movement parallel to the mandrel.
This method does not yield the desired results when the polymer solution is liquid because, when the injection of biologically active medium is interrupted, a drop of polymer solution forms under the die, deforms and breaks under the effect of the weight of the fibre already formed which hangs from the die.
The object of the invention is to improve the above-described method in such a way as to make it possible to manufacture a segmented tubular capsule from a liquid polymer solution. Another object of the invention is to shape a tubular capsule into a shape that can be directly implanted.